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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - Chromatin3D (Chromatin Dynamics in Development and Disease)

Teaser

Summary

Higher order organization of chromatin results in chromosomes, the main organizing factors in the nucleus that occupy discrete territories. Most nuclear processes occur or at least being initiated onto the chromosomes which makes them the main organizing factors in the nucleus. Several proteins that are involved in the replication of DNA, gene transcription and the processing of RNA are found enriched in discrete focal structures. An emerging question is how these structures assemble and are maintained in the absence of membranes and moreover what are the kinetics of stable binding and/or rapid exchange of their components. This dynamic assembly and modification of chromatin that ultimately leads to shaping the genome and regulating the kinetics of physiological processes lacks mechanistic insights at present. Most technologies that have been developed in the last decade for the study of macromolecular complexes and chromatin dynamics are based on either static views or the average behaviour of molecular ensembles leading to the loss of meaningful information. We should also consider that the modifications of individual chromatin components are not as important as the resulting chromatin structure they establish. It is then imperative to develop technologies to accurately measure chromatin compaction, chromatin structure and chromosome associations in cells and even better in individual cells. Such technologies include several modifications of the Chromosome Conformation Capture technology, which is widely applied in several participating laboratories of this network. Such approaches will help us deduce the chromosome domain structure and the involvement of distinct chromatin modification patterns. One step further is the understanding on how these domains influence chromatin fibre association with subnuclear entities and how these associations alter during developmental processes and cell differentiation. Moreover, abnormal expression patterns or genomic alterations in chromatin regulators can lead to the alteration of the overall three-dimensional structure of the genome leading to the induction and maintenance of various malignancies such as cancer, aging or autoimmune diseases.
The overall objectives of Chromatin3D are:
â€¢ To establish a European research platform of excellence in the field of chromatin dynamics and its impact on development and disease by integrating research from basic mechanisms to translational research applications.
â€¢ To create a Network dedicated to the training of young researchers promoting their independent careers, their own scientific goals and future employment prospects.
â€¢ To build durable links between the participating academic and non-academic organisations that will last beyond the duration of Chromatin3D.

Work performed

On 11.03.2015 we posted the position for recruiting a Project Manager for Chromatin3D-642934 with a deadline on 18.03.2015. The Project Manager signed a contract with the coordinator (FORTH) on 01.04.2015. The Consortium Agreement included all amendments/suggestions provided by all beneficiaries and has been signed in February 2015. The text for the Chromatin3Dâ€™s open positions posts (for 15 ESRs) have been sent out on the 20th of February 2015 and has been published by February 24th 2015 in six different websites. 15 ESRs have been recruited in the programme. The Kick off Meeting took place on the first day of month 5 of the programme (01.05.2015) after all beneficiaries have signed the Grant Agreement, the Consortium Agreement has been prepared and signed by all beneficiaries and the funds have been released by the funding authority and later distributed by the coordinator (FORTH). An Amendment to the Chromatin3D-622934 Grant Agreement was launched by the coordinator on 04.09.2015. The First Annual Network meeting took place in Milan, within the premises of IIT (Center for Genomic Science of IIT@SEMM, Istituto Italiano di Tecnologia, Via Adamello 16 â€“ 20139 Milan) on February 03-05 2016. According to Part B of the Grant Agreement the First Annual Network Meeting should be organized on month 6 of the programme by Karolinska Institutet in Stockholm. The First Annual Meeting was organized on month 14 of the programme since the recruitment of all ESRs has been completed on month 12. Also it was decided by all participants during the Kick-off meeting of the network that the first annual meeting should not be organized in Stockholm during the winter due to the weather conditions and it was suggested to take place in Milan and organized by IIT. Following the Annual network meeting, on 04.02.2016 the workshop entitled â€œFolding chromatin in Three dimensionsâ€ took place in IIT/Milan. All network participants were present and attendees also included external participants. In total around 200 attendees participated in the workshop. Day 3 of the Annual network meeting was dedicated to the training of the 15 Chromatin3D ESRs. The course on â€œProject Managementâ€ was delivered by the instructors Susanne Hollmann and Babette Regierer from the Chromatin3D Participating Organization LifeGlimmer. The course was divided in four sessions that lasted the whole day 3 of the meeting.

Final results

The Chromatin3D Network will bring together European institutions, the industry and students. This unique combination of talents will increase the overall quality of academic and industrial training of young European researchers, which will be formed in Europe and will likely continue to deliver their knowledge within Europe in the future. The long-term implications on the fellowsâ€™ career prospects are significant:
1. The training program will enable ESRs to develop and further extend a solid scientific basis, critical judgement and discipline in their research activities allowing them to reach scientific maturity and independence.
2. The combination of basic biology and cutting-edge technologies of the training programme will ensure that the fellows will graduate as a new breed of scientists trained in facing the challenges of contemporary post-genomic biology using advanced technological tools that are widely applicable in both academia and industry, thereby substantially enhancing their research career prospects.
3. A well-worked system of workshops (Table 2.2b), secondments and ESRsâ€™ group integration within the Network (described in each project in Table 4.1d) demonstrates how the network\'s potential will be exploited for the benefit of ESRs over and above that which could be provided in a narrow, national context. This way, Chromatin3D works towards restructuring doctoral training in Europe (by mutual recognition of one another\'s training modules) that could possibly even lead to joint qualifications in the future and to training collaborations beyond the end of the ETN funding period.
4. The effective implementation of complementary skills offered (section B.2.2.5) to the training programme will enable the ESRs to tackle issues that are relevant, no matter what path their research or professional careers will take e.g. technology transfer for a career in biotechnology or clinical studies etc.